Effects of aldosterone on transient outward K+ current density in rat ventricular myocytes

摘要

class="enumerated" style="list-style-type:decimal">Aldosterone, a major ionic homeostasis regulator, might also regulate cardiac ion currents. Using the whole-cell patch-clamp technique, we investigated whether aldosterone affects the 4-aminopyridine-sensitive transient outward K⁺ current (Ito1).Exposure to 100 nm aldosterone for 48 h at 37 °C produced a 1.6-fold decrease in the Ito1 density compared to control myocytes incubated without aldosterone. Neither the time- nor voltage-dependent properties of the current were significantly altered after aldosterone treatment. RU28318 (1 μm), a specific mineralocorticoid receptor antagonist, prevented the aldosterone-induced decrease in Ito1 density.When myocytes were incubated for 24 h with aldosterone, concentrations up to 1 μm did not change Ito1 density, whereas L-type Ca²⁺ current (ICa,L) density increased. After 48 h, aldosterone caused a further increase in ICa,L. The delay in the Ito1 response to aldosterone might indicate that it occurs secondary to an increase in ICa,L.After 24 h of aldosterone pretreatment, further co-incubation for 24 h either with an ICa,L antagonist (100 nm nifedipine) or with a permeant Ca²⁺ chelator (10 μm BAPTA-AM) prevented a decrease in Ito1 density.After 48 h of aldosterone treatment, we observed a 2.5-fold increase in the occurrence of spontaneous Ca²⁺ sparks, which was blunted by co-treatment with nifedipine.We conclude that aldosterone decreases Ito1 density. We suggest that this decrease is secondary to the modulation of intracellular Ca²⁺ signalling, which probably arises from the aldosterone-induced increase in ICa,L. These results provide new insights into how cardiac ionic currents are modulated by hormones.